Summary of Study ST003300
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002050. The data can be accessed directly via it's Project DOI: 10.21228/M8MZ4N This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST003300 |
| Study Title | Hypothalamic SLC7A14 accounts for aging-reduced lipolysis in white adipose tissue |
| Study Summary | The central nervous system has been implicated in the age-induced reduction in adipose tissue lipolysis. SLC7A14 is a lysosomal membrane protein highly expressed in the brain. Herein, we investigated the possible role of hypothalamic SLC7A14 in the age-induced lipolysis reduction. In this study, we demonstrated the expression of SLC7A14 was reduced in proopiomelanocortin (POMC) neurons of aged mice. Overexpression of SLC7A14 in POMC neurons alleviated the age-induced reduction in white adipose tissue (WAT) lipolysis, whereas SLC7A14 deletion mimicked the age-induced lipolysis impairment. Moreover, POMC SLC7A14 regulated WAT lipolysis independently of sympathetic nerves in WAT. Metabolomics analysis revealed that POMC SLC7A14 increased the primary bile acid taurochenodeoxycholic acid (TCDCA) content, which mediated the SLC7A14 knockout- or age-induced WAT lipolysis impairment. Furthermore, SLC7A14-increased TCDCA content is dependent on intestinal apical sodium-dependent bile acid transporter (ASBT), which is regulated by intestinal sympathetic afferent nerves. Finally, SLC7A14 regulated the intestinal sympathetic afferent nerves by inhibiting mTORC1 signaling through inhibiting TSC1 phosphorylation. Collectively, our study suggests the function for central SLC7A14 and an upstream mechanism for the mTORC1 signaling pathway. Moreover, our data provides insights into the brain–gut–adipose tissue crosstalk in age-induced lipolysis impairment. |
| Institute | Shanghai Institutes for Biological Sciences (SIBS) Chinese Academy of Sciences (CAS) |
| Last Name | Liu |
| First Name | Kan |
| Address | No. 320, Yueyang Road, Shanghai |
| liukan2019@sibs.ac.cn | |
| Phone | 021-17718134725 |
| Submit Date | 2024-05-13 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-07-15 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002050 |
| Project DOI: | doi: 10.21228/M8MZ4N |
| Project Title: | Hypothalamic SLC7A14 accounts for aging-reduced lipolysis in white adipose tissue |
| Project Type: | Mass spectrometry |
| Project Summary: | The central nervous system has been implicated in the age-induced reduction in adipose tissue lipolysis. SLC7A14 is a lysosomal membrane protein highly expressed in the brain. Herein, we investigated the possible role of hypothalamic SLC7A14 in the age-induced lipolysis reduction. In this study, we demonstrated the expression of SLC7A14 was reduced in proopiomelanocortin (POMC) neurons of aged mice. Overexpression of SLC7A14 in POMC neurons alleviated the age-induced reduction in white adipose tissue (WAT) lipolysis, whereas SLC7A14 deletion mimicked the age-induced lipolysis impairment. Moreover, POMC SLC7A14 regulated WAT lipolysis independently of sympathetic nerves in WAT. Metabolomics analysis revealed that POMC SLC7A14 increased the primary bile acid taurochenodeoxycholic acid (TCDCA) content, which mediated the SLC7A14 knockout- or age-induced WAT lipolysis impairment. Furthermore, SLC7A14-increased TCDCA content is dependent on intestinal apical sodium-dependent bile acid transporter (ASBT), which is regulated by intestinal sympathetic afferent nerves. Finally, SLC7A14 regulated the intestinal sympathetic afferent nerves by inhibiting mTORC1 signaling through inhibiting TSC1 phosphorylation. Collectively, our study suggests the function for central SLC7A14 and an upstream mechanism for the mTORC1 signaling pathway. Moreover, our data provides insights into the brain–gut–adipose tissue crosstalk in age-induced lipolysis impairment. |
| Institute: | Shanghai Institutes for Biological Sciences (SIBS) Chinese Academy of Sciences (CAS) |
| Last Name: | Liu |
| First Name: | Kan |
| Address: | No. 320, Yueyang Road, Shanghai, Shanghai, Shanghai/Shanghai/xuhui, 200000, China |
| Email: | liukan2019@sibs.ac.cn |
| Phone: | 021-17718134725 |
Subject:
| Subject ID: | SU003421 |
| Subject Type: | Mammal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
| Gender: | Male |
| Species Group: | Mammals |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Genotype | Treatment |
|---|---|---|---|
| SA358120 | QC2 | QC | control |
| SA358121 | QC1 | QC | control |
| SA358122 | QC3 | QC | control |
| SA358123 | oe1 | SLC7A14_OE | control |
| SA358124 | oe2 | SLC7A15_OE | control |
| SA358125 | oe3 | SLC7A16_OE | control |
| SA358126 | oe4 | SLC7A17_OE | control |
| SA358127 | control3 | WT | control |
| SA358128 | control1 | WT | control |
| SA358129 | control2 | WT | control |
| SA358130 | control4 | WT | control |
| SA358131 | control5 | WT | control |
| Showing results 1 to 12 of 12 |
Collection:
| Collection ID: | CO003414 |
| Collection Summary: | Blood was collected from control or overexpression of SLC7A14 in POMC neuron mice.Blood sample was collected into a BD Vacutainer tube not containing any anticoagulant, which was allowed to sit for ~30–60 min for clots to form following which serum was obtained by centrifugation (15 min at 4°C at 3500 rpm). |
| Sample Type: | Blood (serum) |
Treatment:
| Treatment ID: | TR003430 |
| Treatment Summary: | To overexpression of SLC7A14 in ARC POMC neurons, POMC Cre mice were bilaterally injected either with a Cre-dependent AAV vector containing SLC7A14 in the opposite orientation flanked by two inverted loxP sites (AAV9-Syn-DIO-SLC7A14-mCherry, 1.5 × 1012 Pfu/mL, HANBIO) at a volume of 200 nL into the ARC or an AAV vector containing only mCherry in the opposite orientation flanked by two inverted loxP sites (AAV9-Syn-DIO-mCherry, 1.5 × 1012 Pfu/mL, HANBIO) as a control. Serum was collected from control or overexpression of SLC7A14 in POMC neuron mice. |
Sample Preparation:
| Sampleprep ID: | SP003428 |
| Sampleprep Summary: | The samples (100 μL) were placed in the EP tubes and resuspended with prechilled 80% methanol and 0.1% formic acid by well vortex. Then the sampleswere incubated on ice for 5 min and centrifuged at 15,000 g, 4°C for 20 min. Some of supernatant was diluted to final concentration containing 53% methanol by LC-MS grade water.The samples were subsequently transferred to a fresh Eppendorf tube and then were centrifuged at 15000 g, 4°C for 20 min. Finally, the supernatant was injected into the LC-MS/MS system analysis |
Chromatography:
| Chromatography ID: | CH004100 |
| Instrument Name: | Thermo Vanquish |
| Column Name: | Thermo Hypersil GOLD aQ (100 x 2.1mm,1.9um) |
| Column Temperature: | 40°C |
| Flow Gradient: | 2% B, 1.5 min; 2-100% B, 12.0 min; 100% B, 14.0 min；100-2% B, 14.1 min；2% B, 17 min. |
| Flow Rate: | 0.2 mL/min |
| Solvent A: | 100% Water; 5mM Ammonium acetate |
| Solvent B: | 100% Methanol |
| Chromatography Type: | Reversed phase |
Analysis:
| Analysis ID: | AN005407 |
| Analysis Type: | MS |
| Chromatography ID: | CH004100 |
| Has Mz: | 1 |
| Has Rt: | 1 |
| Rt Units: | Minutes |
| Results File: | ST003300_AN005407_Results.txt |
| Units: | Peak area |
